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regulator of G-protein signaling 19

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Target not currently curated in GtoImmuPdb

Target id: 2802

Nomenclature: regulator of G-protein signaling 19

Abbreviated Name: RGS19

Family: RZ family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 217 20q13.33 RGS19 regulator of G protein signaling 19
Mouse - 216 2 103.72 cM Rgs19 regulator of G-protein signaling 19
Rat - 216 3q43 Rgs19 regulator of G-protein signaling 19
Previous and Unofficial Names Click here for help
GAIP | RGSGAIP
Database Links Click here for help
Alphafold P49795 (Hs), Q9CX84 (Mm), O70521 (Rn)
CATH/Gene3D 1.10.196.10
ChEMBL Target CHEMBL3707468 (Hs)
Ensembl Gene ENSG00000171700 (Hs), ENSMUSG00000002458 (Mm), ENSRNOG00000016547 (Rn)
Entrez Gene 10287 (Hs), 56470 (Mm), 59293 (Rn)
Human Protein Atlas ENSG00000171700 (Hs)
KEGG Gene hsa:10287 (Hs), mmu:56470 (Mm), rno:59293 (Rn)
OMIM 605071 (Hs)
Pharos P49795 (Hs)
RefSeq Nucleotide NM_005873 (Hs), NM_001291205 (Mm), NM_021661 (Rn)
RefSeq Protein NP_005864 (Hs), NP_001278134 (Mm), NP_067693 (Rn)
UniProtKB P49795 (Hs), Q9CX84 (Mm), O70521 (Rn)
Wikipedia RGS19 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of human GAIP (Galpha interacting protein): a regulator of G protein signaling.
PDB Id:  1CMZ
Resolution:  0.0Å
Species:  Human
References:  2
Associated Proteins Click here for help
G Proteins
Name References
Go 1
Gi3 3,5,8,38
Gi1 37
Interacting Proteins
Name Effect References
Nm23H1/2 Acts as the scaffold protein or a signal transducer 30
receptor interacting serine/threonine kinase 3 38
GIPC Scaffold protein 15
IPN RGS19 functions as a bifunctional adaptor that binds to G α subunits through its RGS domain and to GIPN through its cysteine string motif. 7
Neurabin Scaffold protein 34
Spinophilin (PPP1R9B) Scaffold protein 35

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CCG-50014 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 26
⤷ pIC50 6.0 (IC50 1.1x10-6 M) [26]
Tissue Distribution Click here for help
Intestine
Species:  Human
Technique:  Northern blot
References:  22
Monocytes and monocytes derived dendritic cells
Species:  Human
Technique:  RT-PCR
References:  27
Ubiquitous expression
Species:  Human
Technique:  RT-PCR
References:  40
Bone marrow-derived dendritic cells
Species:  Mouse
Technique:  RT-PCR
References:  27
Palate (Comment: At E12, epithelial expression of RGS19 is examined in the edge of the palatal shelf. At E13, restricted epithelial expression of RGS19 is observed along the MEE region. At E13.5, RGS19 is expressed in the MEE region in the elevated palatal shelves. At E14, weak and broad expression pattern of RGS19 is examined in the contacting palatal shelves of the middle part of palate.)
Species:  Mouse
Technique:  In situ hybridization
References:  28
Ubiquitous expression
Species:  Mouse
Technique:  RT-PCR
References:  40-41
Brain
Species:  Mouse
Technique:  RT-PCR, western blot
References:  9
Atrial myocytes
Species:  Rat
Technique:  RT-PCR
References:  4
Brain
Species:  Rat
Technique:  In situ hybridisation, RT-PCR
References:  15,33
Brain (the expression levels were highest in the hippocampal formation)
Species:  Rat
Technique:  In situ hybridization,
References:  10
Functional Assays Click here for help
GAP activity
Species:  None
Tissue:  In vitro biochemical assay with purified proteins
Response measured:  Measuring GTP hydrolysis using [γ-32P]GTP
References:  8,24
gGuanine nucleotide dissociation inhibitor (GDI) activity (BODIPY-GTPγS assays)
Species:  Human
Tissue:  HEK293T cells
Response measured:  The rate of incorporation of a poorly hydrolyzable fluorescent GTP analogue by Gαo
References:  19
Inhibition of LPA signaling
Species:  Human
Tissue:  Ovarian cancer Caov-3 cells
Response measured:  Inositol phosphate production by phospholipase C (PLC) enzymes
References:  12
Physiological Functions Click here for help
Acts as GAP for Gq signaling.
Species:  None
Tissue:  In vitro biochemistry ATP hydrolysis assay
References:  11
Suppresses Ras-mediated signaling.
Species:  Human
Tissue:  HEK293 cells
References:  30-31,36
enhances Akt signaling.
Species:  Human
Tissue:  HEK293 cells, Caco2 cells
References:  31
RGS19 regulates Wnt–β-catenin signaling.
Species:  Mouse
Tissue:  F9 embryonic teratocarcinoma cells
References:  6
RGS19 regulates morphine signaling.
Species:  Human
Tissue:  SH-SY5Y cells
References:  33
RGS19 regulates LPA signaling.
Species:  Human
Tissue:  Ovarian cancer Caov-3 cells
References:  12
Modulation of 5-HT1A receptor signaling
Species:  Mouse
Tissue:  SH-SY5Y cells
References:  32
Modulation of 5-HT1A signaling.
Species:  Rat
Tissue:  Brain glial C6 cells
References:  32
Attenuation of μ opioid receptor-mediated inhibition of AC activity.
Species:  Human
Tissue:  HEK293 cells
References:  42
Attenuation of μ opioid receptor activity
Species:  Mouse
Tissue:  Brain CNS
References:  9
RGS19 functions as an essential part of the membrane budding machinery for a subset of post-Golgi exocytic carriers derived from the trans-Golgi network.
Species:  Human
Tissue:  HeLa cells
References:  39
Physiological Consequences of Altering Gene Expression Click here for help
RGS19 deregulates cell cycle gene expression in mouse ESCs.
Species:  Mouse
Tissue:  Embryonic stem cells
Technique:  Gene knockout
References:  16
Knockdown of RGS19 affects palatal fusion through cellular events including cell proliferation and apoptosis and altered expression patterns of EMT related genes.
Species:  Mouse
Tissue:  Mouse embryos
Technique:  Antisense-oligodeoxynucleotide (AS-ODN)
References:  28
RGS19+/- ESCs have decreased proliferation and differentiation in vitro, and decreased tumorigenicity, differentiation and angiogenesis in teratoma formation in vivo.
Species:  Mouse
Tissue:  Embryonic stem cells
Technique:  Gene knockout
References:  16
Transient and stable overexpression of RGS19 upregulates the Nm23-H1/2 protein levels and activates several transcription factors including CRE, AP-1, and SRE in HEK293 cells.
Species:  Human
Tissue:  HEK293 cells
Technique:  Transient and stable overexpression
References:  18
Knockdown of RGS19 diminishes the expression of genes induced by desferrioxamine (DFO) and overexpression of RGS19 enhances the expression of these genes.
Species:  Human
Tissue:  HelLa cells
Technique:  Transient overexpression, shRNA
References:  13
Overexpression of RGS19 decreases cell viability.
Species:  Human
Tissue:  HeLa, SW480 cells
Technique:  Transient overexpression
References:  13
Knockdown of RGS19 results in reduced cell proliferation and overexpression of RGS19 enhances cell proliferation.
Species:  Human
Tissue:  HeLa, HEK293, PC12, Caco2, NIH3T3 cells
Technique:  Stable overexpression, shRNA, siRNA
References:  29,31
Overexpression of RGS19 can lead to the deregulation of cell cycle and knockdown of RGS19 can reverse this change.
Species:  Human
Tissue:  HEK293, Caco2 cells
Technique:  Stable overexpression, siRNA
References:  31
Overexpression of RGS19 is found to attenuate Wnt-responsive gene transcription in a time- and dose-dependent manner, to block cytosolic β-catenin accumulation and Dishevelled3 (Dvl3) phosphorylation in response to Wnt3a and to inhibit Wnt-induced formation of primitive endoderm (PE). However, knockdown of RGS19 also suppresses canonical Wnt signaling.
Species:  Mouse
Tissue:  F9 embryonic teratocarcinoma cells
Technique:  Transient overexpression, siRNA
References:  6
Overexpression of RGS19 suppresses the Rac1/Cdc42-induced phosphorylation of JNK and p38 MAPK, as well as their corresponding upstream and downstream regulators.
Species:  Human
Tissue:  HEK293 cells
Technique:  Stable overexpression
References:  14
Overexpression of RGS19 inhibits cardiomyocyte differentiation by blocking the Wnt signaling in P19 teratocarcinoma cells. In RGS19-overexpressing transgenic (RGS19 TG) mice, impaired cardiac development and function are also observed.
Species:  Mouse
Tissue:  P19 teratocarcinoma cells, heart (isolated at embryonic stages, postnatal stage, and adult)
Technique:  stable overexpression, knock-in
References:  17
Silencing of RGS19 decreases Akt phosphorylation in LPS-stimulated macrophages.
Species:  Mouse
Tissue:  RAW264.7 macrophages
Technique:  siRNA
References:  25
Silencing RGS19 results in increased cell death with or without LPS treatment in macrophages.
Species:  Mouse
Tissue:  RAW264.7 macrophages
Technique:  siRNA
References:  25
Knockdown of RGS19 promotes pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-(OMe)-fluoromethyl ketone (zVAD) induced cell death and inhibits both zVAD- and TNF-induced autophagy.
Species:  Mouse
Tissue:  L929 fibrosarcoma cells
Technique:  shRNA
References:  38
Overexpression of RGS19 inhibits RasGV-induced cell proliferation and neoplastic transformation in vitro and RasGV-induced tumorigenesis in nude mice.
Species:  Mouse
Tissue:  NIH3T3 fibroblasts
Technique:  Stable overexpression
References:  36
Knockdown of RGS19 enhanced tumorigenesis of H1299 cells but impaired tumorigenesis of HeLa cells.
Species:  Human
Tissue:  H1299 cells and Hela cells (xenograft mouse model)
Technique:  shRNA
References:  36
Overexpression of RGS19 stimulated protein degradation along the macroautophagic pathway.
Species:  Human
Tissue:  HT-29 cells
Technique:  Transient transfection
References:  22
Xenobiotics Influencing Gene Expression Click here for help
The endogenous protein level of RGS19 is increased by desferrioxamine (DFO) treatment in a dose-dependent manner while transcription level remains unchanged.
Species:  Human
Tissue:  HeLa cells
Technique:  Western blot, RT-PCR
References:  13
The proteasome inhibitor MG132 increases RGS19 protein level.
Species:  Human
Tissue:  HeLa cells
Technique:  Western blot
References:  13
Co-expression of GIPN significantly decreases the expression level of His-RGS19
Species:  Human
Tissue:  HeLa cells
Technique:  Western blot
References:  13
RGS19 protein, but not mRNA, is increased by overnight treatment with DAMGO (DA), DPDPE (DP), morphine (Mor), or SNC80 (SNC), which can be blocked by PTX, NLX, actinomycin D.
Species:  Human
Tissue:  SH-SY5Y cells
Technique:  Western blot, RT-PCR
References:  33
Treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA) increases RGS19 protein expression level.
Species:  Human
Tissue:  SH-SY5Y cells
Technique:  Western blot
References:  33
Both RGS19 mRNA and protein expression levels are repressed by JQ1 treatment in 786-o and SU-R-786-o cells.
Species:  Human
Tissue:  786-o cells
Technique:  Western blot, RT-PCR
References:  23
Chronic intermittent ethanol exposure increases mRNA and protein levels of RGS19 in rat PFC.
Species:  Rat
Tissue:  Prefrontal cortex
Technique:  RT-PCR, western blot
References:  21
RGS19 is downregulated by quercetin treatment in a dose-dependent manner.
Species:  Human
Tissue:  Neuroglioma cells
Technique:  Western blot
References:  20
Biologically Significant Variants Click here for help
Type:  mRNA alternative splicing
Species:  Mouse
Description:  This N-terminally truncated variant (AF535870) of the mouse GAIP/RGS19 lacks selectivity of full-length GAIP/RGS19 protein in regulating ORL1 receptor signaling over other opioid receptors.
References:  41

References

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2. de Alba E, De Vries L, Farquhar MG, Tjandra N. (1999) Solution structure of human GAIP (Galpha interacting protein): a regulator of G protein signaling. J Mol Biol, 291 (4): 927-39. [PMID:10452897]

3. De Vries L, Mousli M, Wurmser A, Farquhar MG. (1995) GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain. Proc Natl Acad Sci U S A, 92 (25): 11916-20. [PMID:8524874]

4. Doupnik CA, Xu T, Shinaman JM. (2001) Profile of RGS expression in single rat atrial myocytes. Biochim Biophys Acta, 1522 (2): 97-107. [PMID:11750060]

5. Elenko E, Fischer T, Niesman I, Harding T, McQuistan T, Von Zastrow M, Farquhar MG. (2003) Spatial regulation of Galphai protein signaling in clathrin-coated membrane microdomains containing GAIP. Mol Pharmacol, 64 (1): 11-20. [PMID:12815156]

6. Feigin ME, Malbon CC. (2007) RGS19 regulates Wnt-beta-catenin signaling through inactivation of Galpha(o). J Cell Sci, 120 (Pt 19): 3404-14. [PMID:17855383]

7. Fischer T, De Vries L, Meerloo T, Farquhar MG. (2003) Promotion of G alpha i3 subunit down-regulation by GIPN, a putative E3 ubiquitin ligase that interacts with RGS-GAIP. Proc Natl Acad Sci USA, 100 (14): 8270-5. [PMID:12826607]

8. Garcia-Marcos M, Ghosh P, Ear J, Farquhar MG. (2010) A structural determinant that renders G alpha(i) sensitive to activation by GIV/girdin is required to promote cell migration. J Biol Chem, 285 (17): 12765-77. [PMID:20157114]

9. Garzón J, Rodríguez-Muñoz M, López-Fando A, García-España A, Sánchez-Blázquez P. (2004) RGSZ1 and GAIP regulate mu- but not delta-opioid receptors in mouse CNS: role in tachyphylaxis and acute tolerance. Neuropsychopharmacology, 29 (6): 1091-104. [PMID:14997173]

10. Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ. (2001) Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res, 88 (1-2): 113-23. [PMID:11295237]

11. Hepler JR, Berman DM, Gilman AG, Kozasa T. (1997) RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha. Proc Natl Acad Sci U S A, 94 (2): 428-32. [PMID:9012799]

12. Hurst JH, Mendpara N, Hooks SB. (2009) Regulator of G-protein signalling expression and function in ovarian cancer cell lines. Cell Mol Biol Lett, 14 (1): 153-74. [PMID:18979070]

13. Hwang J, Kim HS, Kang BS, Kim DH, Ryoo ZY, Choi SU, Lee S. (2015) RGS19 converts iron deprivation stress into a growth-inhibitory signal. Biochem Biophys Res Commun, 464 (1): 168-75. [PMID:26116529]

14. Ip AK, Tso PH, Lee MM, Wong YH. (2012) Elevated expression of RGS19 impairs the responsiveness of stress-activated protein kinases to serum. Mol Cell Biochem, 362 (1-2): 159-68. [PMID:22045062]

15. Jeanneteau F, Guillin O, Diaz J, Griffon N, Sokoloff P. (2004) GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling. Mol Biol Cell, 15 (11): 4926-37. [PMID:15356268]

16. Ji YR, Kim HJ, Park SJ, Bae KB, Park SJ, Jang WY, Kang MC, Jeong J, Sung YH, Choi M et al.. (2015) Critical role of Rgs19 in mouse embryonic stem cell proliferation and differentiation. Differentiation, 89 (1-2): 42-50. [PMID:25766428]

17. Ji YR, Kim MO, Kim SH, Yu DH, Shin MJ, Kim HJ, Yuh HS, Bae KB, Kim JY, Park HD et al.. (2010) Effects of regulator of G protein signaling 19 (RGS19) on heart development and function. J Biol Chem, 285 (37): 28627-34. [PMID:20562099]

18. Li Y, Song J, Tong Y, Chung SK, Wong YH. (2017) RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation via the cAMP/PKA/CREB pathway. Oncotarget, 8 (41): 69945-69960. [PMID:29050254]

19. Lin C, Koval A, Tishchenko S, Gabdulkhakov A, Tin U, Solis GP, Katanaev VL. (2014) Double suppression of the Gα protein activity by RGS proteins. Mol Cell, 53 (4): 663-71. [PMID:24560274]

20. Lou M, Zhang LN, Ji PG, Feng FQ, Liu JH, Yang C, Li BF, Wang L. (2016) Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuroglioma cells: In vitro and in vivo. Biomed Pharmacother, 84: 1-9. [PMID:27621033]

21. Luessen DJ, Sun H, McGinnis MM, McCool BA, Chen R. (2017) Chronic intermittent ethanol exposure selectively alters the expression of Gα subunit isoforms and RGS subtypes in rat prefrontal cortex. Brain Res, 1672: 106-112. [PMID:28736108]

22. Ogier-Denis E, Petiot A, Bauvy C, Codogno P. (1997) Control of the expression and activity of the Galpha-interacting protein (GAIP) in human intestinal cells. J Biol Chem, 272 (39): 24599-603. [PMID:9305927]

23. Sakaguchi T, Yoshino H, Sugita S, Miyamoto K, Yonemori M, Osako Y, Meguro-Horike M, Horike SI, Nakagawa M, Enokida H. (2018) Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma. Oncotarget, 9 (33): 23003-23017. [PMID:29796168]

24. Salem-Mansour D, Asli A, Avital-Shacham M, Kosloff M. (2018) Structural motifs in the RGS RZ subfamily combine to attenuate interactions with Gα subunits. Biochem Biophys Res Commun, 503 (4): 2736-2741. [PMID:30111488]

25. Sangphech N, Osborne BA, Palaga T. (2014) Notch signaling regulates the phosphorylation of Akt and survival of lipopolysaccharide-activated macrophages via regulator of G protein signaling 19 (RGS19). Immunobiology, 219 (9): 653-60. [PMID:24775271]

26. Shaw VS, Mohammadiarani H, Vashisth H, Neubig RR. (2018) Differential Protein Dynamics of Regulators of G-Protein Signaling: Role in Specificity of Small-Molecule Inhibitors. J Am Chem Soc, 140 (9): 3454-3460. [PMID:29460621]

27. Shi GX, Harrison K, Han SB, Moratz C, Kehrl JH. (2004) Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: implications for G protein-coupled receptor signaling. J Immunol, 172 (9): 5175-84. [PMID:15100254]

28. Sohn WJ, Ji YR, Kim HS, Gwon GJ, Chae YM, An CH, Park HD, Jung HS, Ryoo ZY, Lee S et al.. (2012) Rgs19 regulates mouse palatal fusion by modulating cell proliferation and apoptosis in the MEE. Mech Dev, 129 (9-12): 244-54. [PMID:22841956]

29. Tso PH, Wang Y, Wong SY, Poon LS, Chan AS, Wong YH. (2010) RGS19 enhances cell proliferation through its C-terminal PDZ motif. Cell Signal, 22 (11): 1700-7. [PMID:20599498]

30. Tso PH, Wang Y, Yung LY, Tong Y, Lee MM, Wong YH. (2013) RGS19 inhibits Ras signaling through Nm23H1/2-mediated phosphorylation of the kinase suppressor of Ras. Cell Signal, 25 (5): 1064-74. [PMID:23416464]

31. Tso PH, Yung LY, Wang Y, Wong YH. (2011) RGS19 stimulates cell proliferation by deregulating cell cycle control and enhancing Akt signaling. Cancer Lett, 309 (2): 199-208. [PMID:21705135]

32. Wang Q, Terauchi A, Yee CH, Umemori H, Traynor JR. (2014) 5-HT1A receptor-mediated phosphorylation of extracellular signal-regulated kinases (ERK1/2) is modulated by regulator of G protein signaling protein 19. Cell Signal, 26 (9): 1846-52. [PMID:24793302]

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34. Wang X, Zeng W, Kim MS, Allen PB, Greengard P, Muallem S. (2007) Spinophilin/neurabin reciprocally regulate signaling intensity by G protein-coupled receptors. EMBO J, 26 (11): 2768-76. [PMID:17464283]

35. Wang X, Zeng W, Soyombo AA, Tang W, Ross EM, Barnes AP, Milgram SL, Penninger JM, Allen PB, Greengard P et al.. (2005) Spinophilin regulates Ca2+ signalling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors. Nat Cell Biol, 7 (4): 405-11. [PMID:15793568]

36. Wang Y, Tong Y, Tso PH, Wong YH. (2013) Regulator of G protein signaling 19 suppresses Ras-induced neoplastic transformation and tumorigenesis. Cancer Lett, 339 (1): 33-41. [PMID:23911936]

37. Woulfe DS, Stadel JM. (1999) Structural basis for the selectivity of the RGS protein, GAIP, for Galphai family members. Identification of a single amino acid determinant for selective interaction of Galphai subunits with GAIP. J Biol Chem, 274 (25): 17718-24. [PMID:10364213]

38. Wu T, Li Y, Huang D, Han F, Zhang YY, Zhang DW, Han J. (2014) Regulator of G-protein signaling 19 (RGS19) and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell death in L929 cells. PLoS One, 9 (4): e94634. [PMID:24751948]

39. Wylie FG, Lock JG, Jamriska L, Khromykh T, Brown DL, Stow JL. (2003) GAIP participates in budding of membrane carriers at the trans-Golgi network. Traffic, 4 (3): 175-89. [PMID:12656990]

40. Xie GX, Han X, Ito E, Yanagisawa Y, Maruyama K, Sugano S, Suzuki Y, Wang Y, Gabriel A, Stevens SK et al.. (2003) Gene structure, dual-promoters and mRNA alternative splicing of the human and mouse regulator of G protein signaling GAIP/RGS19. J Mol Biol, 325 (4): 721-32. [PMID:12507475]

41. Xie GX, Yanagisawa Y, Ito E, Maruyama K, Han X, Kim KJ, Han KR, Moriyama K, Palmer PP. (2005) N-terminally truncated variant of the mouse GAIP/RGS19 lacks selectivity of full-length GAIP/RGS19 protein in regulating ORL1 receptor signaling. J Mol Biol, 353 (5): 1081-92. [PMID:16219326]

42. Xie Z, Li Z, Guo L, Ye C, Li J, Yu X, Yang H, Wang Y, Chen C, Zhang D et al.. (2007) Regulator of G protein signaling proteins differentially modulate signaling of mu and delta opioid receptors. Eur J Pharmacol, 565 (1-3): 45-53. [PMID:17433292]

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